Vagally mediated cholestatic and choleretic effects of centrally applied Endothelin-1 through ETA receptors

Myrian R. Rodríguez, María Eugenia Sabbatini, Gisela Santella, Cristina Vescina, Marcelo S. Vatta, Liliana G. Bianciotti

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The role of Endothelin-1 (ET-1) in the central nervous system is not fully understood yet although several studies strongly support its neuromodulatory role. A high density of endothelin receptors is present in the dorsal vagal complex that is the major site for the regulation of the digestive function. Therefore in the present study we sought to establish the role of ET-1 in the central regulation of bile secretion in the rat. Intracerebroventricular ET-1 injection exhibited opposite behaviors on spontaneous bile secretion according to the dose administered. Lower doses of ET-1 (1 fM) increased bile flow and bicarbonate excretion whereas higher doses (1 nM) decreased bile flow and bile acid output. Both the choleretic and the cholestatic effects of ET-1 were abolished in animals pretreated with icv BQ-610 (selective ETA antagonist) but not with BQ-788 (selective ETB antagonist). In addition, truncal vagotomy but not adrenergic blockade abolished ET-1 effects on bile secretion. Brain nitric oxide was not involved in ET-1 response since l-NAME pretreatment failed to affect ET-1 actions on the liver. Portal venous pressure was increased by centrally administered ET-1 being the magnitude of the increase similar with low and high doses of the peptide. These results show that centrally applied ET-1 modified different bile flow fractions independent of hemodynamic changes. Lower doses of ET-1 increased bile acid independent flow whereas higher doses decreased bile acid dependent flow. Vagal pathways through the activation of apparently distinct ETA receptors mediated the cholestatic as well as the choleretic effects induced by ET-1. Present findings show that ET-1 participates in the central regulation of bile secretion in the rat and give further insights into the complexity of brain-liver interaction.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalRegulatory Peptides
Volume135
Issue number1-2
DOIs
StatePublished - Jul 15 2006
Externally publishedYes

Keywords

  • Bicarbonate
  • Bile acids
  • Bile flow
  • Glutathione
  • Portal venous pressure

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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